Autism comprises a heterogeneous group of neurodevelopmental disorders characterized by defects in communication and social interaction. A group of nonsyndromic forms of autism is associated with mutations in the neuroligin genes, which encode postsynaptic adhesion molecules. Using a reversible knockout approach, Baudouin et al. investigated the in vivo functions of neuroligin-3 in the mouse cerebellum. Mutant mice showed a major defect in metabotropic glutamate receptor–dependent long-term potentiation, disrupted heterosynaptic competition, and ectopic synapse formation in vivo. These synaptic defects could be rescued by reactivation of the neuroligin gene in the adult.